Substituted-4-(pyrrolo pyrimidin-6-yl)benzenesulphonamide derivatives

ABSTRACT

This invention is directed to selective antagonists of A 2A  and/or A 2B  adenosine receptors having the general formula (I); to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.

This application is a national stage filing under 35 U.S.C. § 371 ofInternational Application No. PCT/EP03/03378, filed on Apr. 1, 2003.This application claims the benefit of priority under 35 U.S.C. § 119 toSpanish Patent Application No. P200200752 filed on Apr. 1, 2002.

The present invention relates to new antagonists of A_(2A) and A_(2B)adenosine receptors. These compounds are useful in the treatment,prevention or suppression of diseases and disorders known to besusceptible of being improved by antagonism of A_(2A) and/or A_(2B)adenosine receptors, such as Parkinson's disease, asthma, allergicdiseases, inflammation, atherosclerosis, hypertension, gastrointestinaltract disorders, cell proliferation disorders and autoimmune diseases.

Adenosine regulates several physiological functions through specificcell membrane receptors, which are members of the G-protein coupledreceptor family. Four distinct adenosine receptors have been identifiedand classified: A₁, A_(2A), A_(2B) and A₃.

A_(2A) adenosine receptors are mainly found in the brain (striatum,nucleus accumbens and olfactory bulb), platelets, leukocytes, spleen andthymus (see Fredholm et al. Pharmacol Rev. 2001, 53 (4), 527-552).Adenosine A_(2A) receptors modulate the release of GABA in the striatum.Thus, A_(2A) receptor antagonists are a useful alternative for thetreatment for Parkinson's disease (Mally, J. and Stone, T. W., CNSDrugs, 1998, 10, 311-320) and for other neurodegenerative diseases. Thepharmacology of A_(2A) adenosine receptors has been reviewed by Onginiet al. in Trends Pharmacol Sci. 1996, 17(10), 364-372.

The A_(2B) adenosine receptor subtype (see Feoktistov, I., Biaggioni, I.Pharmacol. Rev. 1997, 49, 381-402) has been identified in a variety ofhuman and murine tissues and is involved in the regulation of vasculartone, smooth muscle growth, angiogenesis, hepatic glucose production,bowel movement, intestinal secretion, and mast cell degranulation.

In view of the physiological effects mediated by adenosine receptoractivation, several A_(2A) and/or A_(2B) receptor antagonists have beenrecentity disclosed for the treatment or prevention of Parkinson'sdisease, Alzheimer disease, Huntington chorea, Wilson's disease, asthma,bronchoconstriction, allergic diseases, hypertension, atherosclerosis,reperfusion injury, myocardial ischemia, retinopathy, inflammation,gastrointestinal tract disorders, cell proliferation diseases and/ordiabetes mellitus. See for example WO 01/16134, WO 01/02400, WO 01/80893or WO 00/73307.

It has now been found that certain4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives are new potentand selective antagonists of A_(2A) and A_(2B) adenosine receptors andcan therefore be used in the treatment or prevention of these diseases.

Further objectives of the present invention are to provide a method forpreparing said compounds; pharmaceutical compositions comprising aneffective amount of said compounds; the use of the compounds in themanufacture of a medicament for the treatment of pathological conditionsor diseases susceptible of being improved by antagonism of A_(2A) and/orA_(2B) adenosine receptors; and methods of treatment of pathologicalconditions or diseases susceptible to amelioration by antagonism ofA_(2A) and/or A_(2B) adenosine receptors comprising the administrationof the compounds of the invention to a subject in need of treatment.

Thus, the present invention is directed to new6-(4-aminosulphonylphenyl)-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dionederivatives of formula (I)

wherein

-   R¹ and R² each independently represent:-   a hydrogen atom;-   a hydrocarbon chain selected from an alkyl, alkenyl or alkynyl    group, which is optionally substituted by one or more, for example    1, 2, 3 or 4, substituents selected from halogen, hydroxy, alkoxy,    alkylthio, amino, monoalkylamino, dialkylamino, cyano, oxo,    hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl,    alkylcarbamoyl, dihydroxyphosphoryloxy or dialkoxyphosphoryloxy    groups;-   or a group of formula    —(CH₂)_(n)—R⁶-   wherein n is an integer from 0 to 4 and R⁶ represents a 3- to    7-membered aromatic or non-aromatic cyclic group containing from 0    to 4 heteroatoms selected from N, O and S, which is optionally    bridged and/or fused to another 3- to 7-membered aromatic or    non-aromatic cyclic group containing from 0 to 4 heteroatoms    selected from N, O and S;-   the cyclic groups in the moiety R⁶ being optionally substituted by    one or more, for example 1, 2, 3 or 4, R⁷ substituents selected from    halogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl,    heteroaryl, heteroarylalkyl, heterocydyl, hydroxy, alkylenedioxy,    alkoxy, alkylthio, amino, monoalkylamino, dialkylamino, nitro,    cyano, oxo, hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl,    alkylcarbamoyl, dihydroxyphosphoryloxy and dialkoxyphosphoryloxy    groups;-   the hydrocarbon chains and the cyclic moieties of these R⁷    substituents being optionally substituted by one or more, for    example 1, 2, 3 or 4, further R⁸ substituents selected from halogen,    hydroxy, oxo, cyano, alkyl, difluoromethyl, trifluoromethyl, alkoxy,    alkylenedioxy, alkylthio, acylamino, carbamoyl, alkylcarbamoyl,    dihydroxyphosphoryloxy, dialkoxyphosphoryloxy, hydroxyalkoxy,    phenyl, alkoxycarbonyl, amino, monoalkylamino, dialkylamino and    hydroxycarbonyl groups;-   R³ represents a hydrogen or halogen atom, or a nitro, alkoxycarbonyl    or alkyl group; the alkyl group being optionally substituted by one    or more, for example 1, 2, 3 or 4, substituents selected from    hydroxy, alkoxy, alkylthio, amino, monoalkylamino, dialkylamino,    hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl or    alkylcarbamoyl groups;-   R⁴ and R⁵ are the same or different, each independently    representing:-   hydrogen;-   a group of formula —(CH₂)_(n)—R⁶, wherein n is an integer from 0 to    4; and R⁶ is as defined above and is optionally substituted by one    or more, for example 1, 2, 3 or 4, R⁷ substituents, wherein R⁷ is as    defined above and is optionally substituted by one or more, for    example 1, 2, 3 or 4, further R⁸ substituents. wherein R⁸ is as    defined above;-   or a hydrocarbon chain selected from alkyl, alkenyl or alkynyl,    which is optionally substituted by one or more, for example 1, 2, 3    or 4, substituents selected from —(CH₂)_(n)—R⁶, —O—(CH₂)_(n)—R⁶,    —S—(CH₂)_(n)—R⁶, —NH—(CH₂)_(n)—R⁶, hydroxy, oxo, halogen, alkoxy,    alkylthio, amino, monoalkylamino, and dialkylamino groups; the alkyl    chains in the alkoxy, alkylthio, monoalkylamino and dialkylamino    substituents being optionally substituted by one or more, for    example 1, 2, 3 or 4, further substituents selected from    —(CH₂)_(n)—R⁶, hydroxy, oxo, halogen, alkoxy, alkylthio, amino,    monoalkylamino and dialkylamino groups; and wherein each n is    independently an integer from 0 to 4 and each R⁶ is as defined above    and is optionally substituted by one or more, for example 1, 2, 3 or    4, R⁷ substituents, wherein R⁷ is as defined above and is optionally    substituted by one or more, for example 1, 2, 3 or 4, further R⁸    substituents, wherein R⁸ is as defined above;-   or, alternatively, R⁴ and R⁵, together with the nitrogen atom to    which they are attached, form a 3- to 7-membered aromatic or    non-aromatic cyclic group comprising from 1 to 4 heteroatoms    selected from N, O and S, which is optionally bridged and/or fused    to another 3- to 7-membered aromatic or non-aromatic cyclic group    containing from 0 to 4. heteroatoms selected from N, O and S; the    cyclic groups being optionally substituted by one or more, for    example 1, 2, 3 or 4, substituents selected from —(CH₂)_(n)—R⁶ and    R⁷; the hydrocarbon chains and the cyclic moieties of the R⁷    substituents being optionally substituted by one or more, for    example 1, 2, 3 or 4, further substituents selected from    —(CH₂)_(n)—R⁶ and R⁸; and the alkyl chains in the R⁵ substituents    being optionally substituted by one or more, for example 1, 2, 3 or    4, further substitutents selected from —(CH₂)_(n)—R⁶, hydroxy,    halogen, alkoxy, alkylthio, amino, monoalkylamino and dialkylamino    groups; wherein each of the R⁶ substituents is optionallly    substitued by one or more, for example 1, 2, 3 or 4, R⁷ substituents    and each of these R⁷ substituents is optionally substituted by one    or more, for example 1, 2, 3 or 4, R⁸ substituents; and wherein each    n, R₆, R⁷ and R⁸ is as defined above.    or an N-oxide or a pharmaceutically acceptable salt thereof.

As used herein, a hydrocarbon chain is a straight or branched non-cylicsequence of carbon atoms covalently linked by single, double or triplebonds, and substituted by hydrogen atoms, for example straight orbranched alkyl, alkenyl or alkynyl groups, moieties or chains.Typically, the hydrocarbon chains contain from 1 to 10 carbon atoms. Asused herein, an alkyl, alkenyl or alkynyl group or moiety is a straightor branched group or moiety. Typically it is a C₁-C₁₀ group or moiety,for example a C₁-C₆ group or moiety, preferably a C₁-C₄ group or moiety.Examples include methyl, ethyl. i-propyl, n-propyl, n-butyl, t-butyl,allyl, 2-propenyl and 3-butynyl. Where a group contains two or morealkyl, alkenyl or alkynyl moieties, these moieties may be the same ordifferent. When an alkyl, alkenyl or alkynyl chain, group or moietycarries 2 or more substituents, the substituents may be the same ordifferent.

As used herein, an alkylene group or moiety is a divalent alkyl moietytypically having from 1 to 6, for example from 1 to 4, carbon atoms.Examples of C₁-C₄ alkylene groups include methylene, ethylene, propyleneand butylene groups. When an alkylene or alkylenedioxy group is presentas a substituent on another group it shall be deemed to be a singlesubstituent, rather than a group formed by two substituents.

As used herein, the alkyl chains present in the arylalkyl,heteroarylalkyl, alkoxy, alkylthio, monoalkylamino, dialkylamino,hydroxyalkoxy, alkoxycarbonyl, alkylcarbamoyl, alkylenedioxy anddialkoxyphosphoryloxy groups are typically straight or branched alkylchains containing from 1 to 6 carbon atoms.

As used herein, an acyl group or moiety typically has from 2 to 7 carbonatoms. Thus, it is typically a group of formula —COR wherein R is ahydrocarbon chain group having from 1 to 6 carbon atoms. Preferably, itis a group of formula —COR wherein R is a C₁-C₆ alkyl group.

As used herein, an aryl group or moiety is typically a C₆-C₁₀ aryl groupor moiety such as phenyl or naphthyl. Phenyl is preferred. When an arylgroup or moiety carries 2 or more substituents, the substituents may bethe same or different.

As used herein, a heteroaryl group or moiety is typically a 5- to10-membered aromatic ring, such as a 5- or 6-membered ring, containingat least one heteroatom selected from O, S and N. Examples includepyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, furanyl, oxadiazolyl,oxazolyl, imidazolyl, thiazolyl, thiadiazolyl, thienyl, pyrazolidinyl,pyrrolyl and pyrazolyl groups. Oxadiazolyl, oxazolyl, pyridyl, pyrrolyl,imidazolyl, thiazolyl, thiadiazolyl, furanyl, thienyl, pyrazinyl andpyrimidinyl groups are preferred. When a heteroaryl group or moietycarries 2 or more substituents, the substituents may be the same ordifferent.

As used herein, a cycloalkyl group typically has from 3 to 6 carbonatoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl andcyclohexyl. It is preferably cyclopropyl, cyclopentyl or cyclohexyl.When a cycloalkyl group carries 2 or more substituents, the substituentsmay be the same or different.

As used herein, a heterocydyl group is typically a non-aromatic,saturated or unsaturated C₃-C₁₀ carbocydic ring in which one or more,for example 1, 2, 3 or 4 of the carbon atoms are replaced by aheteroatom selected from N, O and S. Saturated heterocydyl groups arepreferred. Examples of suitable heterocyclyl groups include piperidinyl,piperazinyl, morpholinyl, 4,5-dihydro-oxazolyl, 3-aza-tetrahydrofuranyl,imidazoildinyl and pyrrolidinyl groups. Where a heterocyclyl groupcarries 2 or more substituents, the substituents may be the same ordifferent.

As used herein, a halogen atom, is typically a chlorine, fluorine orbromine atom.

As used herein, some of the atoms, groups, moieties, chains or cyclespresent in the general structures of the invention are “optionallysubstituted”. This means that these atoms, groups, moieties, chains orcycles can be either unsubstituted or substituted by one or more, forexample 1, 2, 3 or 4, substituents, whereby the hydrogen atoms bound tothe unsubstituted atoms, groups, moieties, chains or cycles are replacedby chemically acceptable atoms, groups, moieties, chains or cycles.Typically when a cyclic group is bridged by an alkylene group, thebridging alkylene group is attached to the ring at non-adjacent atoms.

Compounds of the formula (I) containing one or more chiral centre may beused in enantiomerically or diastereoisomerically pure form, or in theform of a mixture of isomers.

As used herein, a pharmaceutically acceptable salt is a salt with apharmaceutically acceptable acid or base. Pharmaceutically acceptableacids include both inorganic acids, for example hydrochloric, sulphuric,phosphoric, diphosphoric, hydrobromic and nitric acid and organic acids,for example citric, fumaric, maleic, malic, ascorbic, succinic,tartaric, benzoic, acetic, methanesulphonic, ethanesulphonic,benzenesulphonic or p-toluenesulphonic acid. Pharmaceutically acceptablebases include alkali metal (e.g. sodium or potassium) and alkali earthmetal (e.g. calcium or magnesium) hydroxides and organic bases, forexample alkyl amines, aralkyl amines and heterocyclic amines.

As used herein, an N-oxide is formed from the tertiary basic amines orpyridines present in the molecule, using a convenient oxidising agent.

Preferred compounds of the invention are those wherein R¹ and R² areindependently an alkyl group optionally substituted by one or more, forexample 1, 2, 3 or 4, substituents selected from hydroxy, halogen,alkoxy, alkylthio, amino, monoalkylamino, dialkylamino, hydroxycarbonyl,and alkoxycarbonyl groups; or a group of formula —(CH₂)_(n)—R⁶, whereinn is an integer from 0 to 2 and R⁶ represents a 3- to 7-memberedaromatic or non-aromatic cyclic group having from 0 to 2 heteroatomsselected from nitrogen and oxygen. More preferred compounds are thosewherein the alkyl chains, moieties or groups present R¹ and R² are C₁-C₆alkyl chains, moieties or groups. Most preferably, R¹ and R² are bothunsubstituted C₁-C₆ alkyl groups.

Further preferred compounds of the invention are those wherein R³represents hydrogen or a halogen atom, more preferably hydrogen or achlorine atom, most preferably hydrogen.

Also preferred are compounds wherein R⁴ is as defined above and R⁵ ishydrogen, a group of formula —(CH₂)_(n)—R⁶ or a hydrocarbon chainselected from alkyl, alkenyl and alkynyl, which is optionallysubstituted by one or more, for example 1, 2, 3 or 4, groups selectedfrom —(CH₂)_(n)—R⁶ and —(CH₂)_(n)—O—R⁶; each R⁶ being a phenyl or apyridyl group, which is optionally substituted by one or more, forexample 1, 2, 3 or 4, substituents selected from halogen, hydroxy,alkyl, alkoxy and alkylthio groups. More preferred compounds are thosewherein R⁵ is hydrogen, alkyl or benzyl. Most preferred compounds arethose wherein R⁵ is hydrogen or alkyl.

Typically, R⁴ is:

-   -   hydrogen;    -   a group of formula —(CH₂)_(n)—R⁶, wherein n is 0, 1 or 2 and R⁶        is a 5- to 7-membered aromatic or non-aromatic cyclic group        containing 0 to 2 heteroatoms selected from N, O and S, which is        optionally substituted by one or more, for example 1, 2, 3 or 4,        R⁷ substituents selected from halogen, alkyl, alkenyl, alkynyl,        aryl, arylalkyl, cycloalkyl, heteroaryl, heteroarylalkyl,        heterocyclyl, hydroxy, alkylenedioxy, alkoxy, alkylthio, amino,        monoalkylamino, dialkylamino, nitro, cyano, oxo,        hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl,        alkylcarbamoyl, dihydroxyphosphoryloxy and dialkoxyphosphoryloxy        groups; the hydrocarbon chains and the cyclic moieties of these        R⁷ substituents being optionally substituted by one or more, for        example 1, 2, 3 or 4, further R⁸ substituents selected from        halogen, hydroxy, oxo, cyano, alkya trifluoromethyl, alkoxy,        alkylenedioxy, alkylthio, acylamino, carbamoyl, alkylcarbamoyl,        dihydroxyphosphoryloxy, dialkoxyphosphoryloxy, hydroxyalkoxy,        phenyl, alkoxycarbonyl, amino, monoalkylamino, dialkylamino and        hydroxycarbonyl groups; or    -   an alkyl, alkenyl or alkynyl chain, which is optionally        substituted by one or more, for example 1, 2, 3 or 4,        substituents selected from —(CH₂)_(n)—R⁶, —O—(CH₂)_(n)—R⁶,        —S—(CH₂)_(n)—R⁶, —NH—(CH₂)_(n)—R⁶, hydroxy, oxo, halogen,        alkoxy, alkylthio, amino, monoalkylamino, and dialkylamino        groups; the alkyl chains in the alkoxy, alkylthio,        monoalkylamino and dialkylamino substituents being optionally        substituted by one or more, for example 1, 2, 3 or 4, further        substituents selected from —(CH₂)_(n)—R⁶, hydroxy, oxo, halogen,        alkoxy, alkylthio, amino, monoalkylamino and dialkylamino        groups; and wherein each n is independently an integer from 0 to        4 and each R⁶ is independenty a 5- or 6-membered aromatic or        non-aromatic cyclic group having 0, 1 or 2 heteroatoms selected        from N, O and S, and is optionally substituted by one or more,        for example 1, 2, 3 or 4, R⁷ substituents, wherein R⁷ is as        defined above and is optionally substituted by one or more, for        example 1, 2, 3 or 4, further R⁸ substituents, wherein R⁸ is as        defined above;

More preferably, R⁴ is:

-   -   hydrogen;    -   a group of formula —(CH₂)_(n)—R⁶ wherein n is 0, 1 or 2 and R⁶        is a 5- to 6-membered heteroaryl or heterocyclyl group        containing up to 2 heteroatoms selected from N, O and S, for        example a piperidinyl, pyrrolidinyl or pyridyl group, which is        optionally substituted by a R⁷ substituent selected from        halogen, alkyl, alkoxy, arylalkyl or heteroarylalkyl groups, the        aryl and heteroaryl moieties of these arylalkyl and        heteroarylalkyl R⁷ substituents being optionally substituted by        1 or 2 further R⁸ substituents selected from halogen, cyano,        alkyl, trifluoromethyl, alkoxy and alkylenedioxy; or    -   an alkyl group which is optionally substituted by 1 or 2        substituents selected from amino monoalkylamino, dialkylamino,        —OR⁶ and —SR⁶ substituents, wherein R⁶ is a 5- or 6-membered        heteroaryl group containing 1 or 2 heteroatoms, for example a        pyridyl group, and is optionally substituted by one or more R⁷        substituents selected from hydroxy, halogen, amino,        monoalkylamino, dialkylamino, cyano, hydroxycarbonyl,        alkoxycarbonyl, alkoxy, alkylenedioxy and alkylthio; and wherein        the alkyl chains of each of the said monoalkylamino and        dialkylamino substituents are optionally substituted by 1 or 2        further substituents selected from a hydroxy group and a group        of formula —(CH₂)_(n)—R⁶, wherein n is an integer from 0 to 4        and R⁶ is an aryl group, for example a benzyl group.

Most preferably, R⁴ is:

-   -   a group of formula —(CH₂)_(n)—R⁶ wherein n is 0, 1 or 2 and R⁶        is a 5- to 6-membered heteroaryl or heterocyclyl group        containing up to 2 N atoms, for example a piperidinyl,        pyrrolidinyl or pyridyl group, which is optionally substituted        by a R⁷ substituent selected from halogen, alkyl, alkoxy,        arylalkyl or heteroarylalkyl groups, the aryl and heteroaryl        moieties of these arylalkyl and heteroarylalkyl R⁷ substituents        being optionally substituted by 1 or 2 further R⁸ substituents        selected from halogen and alkoxy; or    -   an alkyl group which is optionally substituted by 1 or 2        substituents selected from monoalkylamino, dialkylamino, —OR⁶        and —SR⁶ substituents, wherein R⁶ is a 5- or 6-membered        heteroaryl group containing 1 or 2 N atoms, for example a        pyridyl group, and is optionally substituted by one or more R⁷        substituents selected from halogen and alkoxy; and wherein the        alkyl chains of each of the said monoalkylamino and dialkylamino        substituents are optionally substituted by 1 or 2 further        substituents selected from a hydroxy group and a group of        formula —(CH₂)_(n)—R⁶, wherein n is an integer from 0 to 4 and        R⁶ is an aryl group, for example a benzyl group.

In other preferred embodiments of the invention R⁴ and R⁵ form, togetherwith the nitrogen atom to which they are attached, an optionally bridged5- to 7-membered aromatic or non-aromatic cyclic group which contains upto two nitrogen atoms, and which is optionally substituted by a group offormula —(CH₂)_(n)—R⁶ or by a R⁷ substituent selected from alkyl,alkenyl and alkynyl chains; the said alkyl, alkenyl and alkynyl chainsbeing optionally substituted by one or more, for example 1, 2, 3 or 4,groups of formula —(CH₂)_(n)—R⁶ or R⁸ substituents selected fromhydroxy, halogen, alkoxy, alkylthio, amino, monoalkylamino, anddialkylarmino groups; the alkyl chains in these R⁸ substituents beingoptionally substituted by one or more, for example 1, 2, 3 or 4, furthersubstituents selected from a group of formula —(CH₂)_(n)—R⁶, andhydroxy, halogen, alkoxy, alkylthio, amino, monoalkylamino anddialkylamino groups; wherein each of the R⁶ groups is optionalllysubstitued by one or more, for example 1, 2, 3 or 4, R⁷ substituents andeach of these R⁷ substituents is optionally substituted by one or more,for example 1, 2, 3 or 4, R⁸ substituents; each n, R⁶, R⁷ and R⁸ beingas defined above.

More preferably, R⁴ and R⁵ form, together with the N atom to which theyare attached, a 5-, 6- or 7-membered saturated heterocyclic group whichcontains 1 or 2 nitrogen atoms and which optionally carries a bridgingalkylene group (for example a piperazinyl, homopiperazinyl, or2,5-methanopiperazinyl group), said cyclic group being optionallysubstituted by a group of formula —(CH₂)_(n)—R⁶ wherein n is 0, 1 or 2and R⁶ is a 5- or 6-membered aromatic or non-aromatic ring containing 0,1 or 2 heteroatoms selected from N, O and S (for example, a phenyl,furanyl, thienyl, pyridyl or pyrimidinyl ring), or by a R⁷ substituentselected from alkyl and alkenyl groups, the group R⁶ being optionallysubstituted by 1, 2 or 3 further substituents selected from haloalkyl,alkyl, alkoxy, alkylenedioxy, cyano and halogen groups, and the said R⁷substituent being optionally substituted by 1 or 2 phenyl substituents.

Particular individual compounds of the invention include:

-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(2,4-Difluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(2-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(2-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Dimethyl-6-{4-[4-(4-trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione-   4-{4-[4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile-   6-[4-(4-Furan-3-ylmethylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Dimethyl-6-[4-(4-thiophen-2-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Dimethyl-6-[4-(4-pyridin-4-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Dimethyl-6-{4-[4-(1-phenylethyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-(4-Benzyl-[1,4]diazepane-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Fluorobenzyl)[1,4]diazepane-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Dimethyl-6-{4-[4-((E)-3-phenylallyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-((1S,4S)-5-Benzyl-2,5-diazabicyclo[2.2.1]heptane-2-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-(4-Benzhydrylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   N-[2-(Benzylmethylamino)ethyl]-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   1,3-Dimethyl-6-[4-(4-pyridin-2-yl-piperazine-1-sulphonyl)-phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(5-Methoxypyrimidin-4-yl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   N-(1-Benzylpiperidin-4-yl)-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(4-fluorobenzyl)piperidin-4-yl]benzenesulphonamide-   N-[1-(3,4-Dimethoxybenzyl)piperidin-4-yl]-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(1-thiophen-2-ylmethylpiperidin-4-yl)benzenesulphonamide-   N-(1-Benzylpiperidin-4-yl)-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methylbenzenesulphonamide-   N-(1-Benzylpyrrolidin-3-yl)-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   N-(1-Benzylpyrrolidin-3-yl)-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methylbenzenesulphonamide-   4-(1,3-Dimethyl-2,4dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-yl)benzenesulphonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylbenzenesulphonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(5-methylpyridin-2-yl)benzenesulphonamide-   1,3-Dimethyl-6-[4-(4-phenylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Dimethyl-6-{4-[4-(4-trifluoromethylphenyl)piperazine-1-sulphonyl]-phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3,5-Dichloropyridin-4-yl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Diethyl-6-{4-[4-(4-fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Diethyl-6-{4-[4-(3-fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(2,4-Difluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pynimidine-2,4-dione-   6-{4-[4-(4-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(2-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Diethyl-6-{4-[4-(4-trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Diethyl-6-{4-[4-(4-methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Diethyl-6-{4-[4-(3-methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-{4-[4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile-   1,3Diethyl-6-[4-(4-furan-2-ylmethylpiperazine1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3Diethyl-6-[4-(4thiophen-2-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piparazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4dione-   1,3-Diethyl-6-[4-(4-pyridinyl-4-methylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Diethyl-6-{4-[4-(1-phenylethyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3Diethyl-6-{4-[4-(4-fluorobenzyl-[1,4]diazepane1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Diethyl-6-[4-(4-phenethylpiperazine-1-sulphonyl)phenyl]-1,5dihydropyrrolo[3,2-d]pyrimidine-2,4dione-   6-[4-((1S,4S)-5-Benzyl-2,5-diazabicyclo[2.2.1]heptane-2-sulphonyl)phenyl]-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   N-[2-(Benzylmethylamino)ethyl]-4-(diethyldioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   N-{2-[Benzyl-(2-hydroxyethyl)amino]ethyl}-4-(diethyldioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimiding-6-yl)benzenesulphonamide-   1,3-Diethyl-6-[4-(4-pyridin-2-ylpiperazine-1-sulphonyl)phenyl]-1,5dihydropyrrolo[3,2-d]pyrimidine-2,4dione-   N-(1-Benzylpiperidin-4-yl)-4-(1,3-diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(4-fluorobenzyl)piperidin-4yl]benzenesulphonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(3,4-dimethoxybenzyl)piperidin-4-yl]benzenesulphonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(1-thiophen-2-ylmethylpiperidin-4-yl)benzenesulphonamide-   N-(1-Benzylpiperidin-4yl)-4-(1,3-diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methylbenzenesulphonamide-   N-(1-Benzylpyrrolidin-3-yl)-4-(1,3-diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   N-(1-Benzylpyrrolidin-3-yl)-4-(1,3diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pydimidin-6-yl)-N-methylbenzenesulphonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-yl-ethyl)benzenesulphonamide-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dipropyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pydimidine-2,4-dione-   6-{4-[4-(2,4-Difluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3dipropyl-1,5-dihydropyrrolo[3,2-d]pydimidine-2,4-dione-   6-{4-[4-(4-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(2-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Dipropyl-6-{4-[4-(4-trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pydimidine-2,4-dione-   6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-{4-[4-(2,4-Dioxo-1,3dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile-   1,3-Dipropyl-6-[4-(4-thiophen-2-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Dipropyl-6-[4-(4-pyridin-4-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(1-Phenylethyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Fluorobenzyly[1,4]diazepane-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-(4-Phenethylpiperazine-1-sulphonyl)phenyl]-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1,3-Dipropyl-6-[4-(4-pyridin-2-ylpiperazine-1-sulphonyl)pheny]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   N-(1-Benzylperidin-4-yl)-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(4-fluorobenzylpiperidin-4-yl]benzenesulphonamide-   N-[1-(3,4-Dimethoxybenzyl)piperidin-4-yl]-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(1-thiophen-2-yl-methylpiperidin-4-yl)benzenesulphonamide-   N-(1-Benzylpiperidin-4-yl)-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methylbenzenesulphonamide-   N-(1-Benzylpyrrolidin-3-yl)-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-yl)benzenesulphonamide-   4-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-yl-ethyl)benzenesulphonamide-   4-(2,4Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylbenzenesulphonamide-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(2,4-Difluorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(2-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1-Methyl-3propyl-6-{4-[4-(4-trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Methoxybenzyl)piparazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6[4-(4-Benzol[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-{4-[4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile-   6-[4-(4-Furan-3-ylmethylpiperazine-1-sulphonyl)phenyl]-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1-Methyl-3-propyl-6-[4-(4-thiophen-2-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1-Methyl-3-propyl-6-[4-(4-pyridin-4-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6{4-[4-(4-Fluorobenzyl)-[1,4]diazepane-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   N-[2-(Benzylmethylamino)ethyl]-4-(methyldioxopropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   1-Methyl-3-propyl-6-[4-(4-pyridin-2-yipiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidin-2,4-dione-   N-(1-Benzylpiperidin-4-yl)-4-(1-methy-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   N-[1-(4-Fluoro-benzyl)piperidin-4-yl]-4-(1-methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   N-[1-3,4Dimethoxybenzyl)piperidin-4-yl]-4-(1-methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(1-thiophen-2-ylmethylpiperidin-4-yl)benzenesulphonamide-   N-(1-Benzylpiperdin-4-yl)-N-methyl-4-(1-methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Fluorobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Fluorobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Chlorobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Chlorobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Bromobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(2-Bromobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   3-Methyl-1-propyl-6-{4-[4-(4-trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-3methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-(4-Benzol[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-{4-[4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile-   3-Methyl-1-propyl-6-[4-(4-thiophen-2-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]-phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   3-Methyl-1-propyl-6-[4-(4-pyridin-4-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   3-Methyl-6-{4-[4-(1-phenylethyl)piperazine-1-sulphonyl]-phenyl}-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2.4-dione-   6-[4-(4-Benzyl[1,4]diazepane-1-sulphonyl)phenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Fluorobenzyl)[1,4]diazepane-1-sulphonyl]-phenyl}-methyl-1-propyl-1,5-dihydropyrrolo[3.2-d]pyrimidine-2,4-dione-   3-Methyl-6-[4-(4-phenethylpiperazine-1-sulphonyl)phenyl]-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2.4-dione-   6-[4-(5-Benzyl-2,5-diazablcyclo[2.2.1]heptane-2-sulphonyl)-phenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   N-[2-(Benzylmethylamino)ethyl]-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   N-{2-[Benzyl-(2-hydroxyethyl)amino]ethyl}-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   3-Methyl-1-propyl-6-[4-(4-pyridin-2-yl-piperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   N-(1-Benzylpiperidin-4-yl)-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3.2-d]pyrimidin-6-yl)benzenesulphonamide-   N-[1-(4-Fuorobenzyl)-piparidin-4-yl]-4-(3-methyl-2,4-dioxo-1-propyl-2.3,4,5-tstrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   N-[1-(3,4-Dimethoxybenzyl)piperidin-4-yl]-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(1-thiophen-2-ylmethylpiperidin-4-yl)benzenesulphonamide-   N-(1-Benzylpiperidin-4-yl)-N-methyl-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-yl-ethyl)benzenesulphonamide-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-7-chloro-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6yl)-N-pyridin-2-ylmethylbenzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-3-ylmethylbenzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-4-ylmethylbenzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-ylmethyl)benzenesulfonamide-   N-(3-Chloropyridin-4-ylmethyl)-4-(1,3-dimethyl-2,4-dioxo-2    3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methyl-N-(2-pyridin-2-ylethyl)benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-3-ylethyl)benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-4-ylethyl)benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]benzenesulfonamide    4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(6-methoxypyridin-2-yloxy)ethyl]benzenesulfonamide    4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(4-methylpyridin-2-yloxy)ethyl]benzenesulfonamide-   N-[2-(5-Chloropyridin-2-yloxy)ethyl]-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(5-trifiuoromethylpyridin-2-yloxy)ethyl]benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-3-yloxy)ethyl]benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyrazin-2-yloxy)ethyl]benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-ylsulfanyl)ethyl]benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyrimidin-2-ylsulfanyl)ethyl]benzenesulfonamide-   N-Benzyl-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]benzenesulfonamide-   N-Benzyl-4-(1,3-dimethy-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6yl)-N-[2-(6-methoxypyridin-2-yloxy)ethyl]benzenesulfonamide-   N-Benzyl-N-[2-(6-chloropyridin-3-yloxy)ethyl]-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulfonarnide-   6-[4-(4-Benzylpiperidine-1-sulfonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Methoxyphenyl)piperidine-1-sulfony]phenyi}-3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylmethylbenzenesulfonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-3-ylmethylbenzenesulfonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-4-ylmethylbenzenesulfonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-ylmethyl)benzenesulfonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methyl-N-(2-pyridin-2-ylethyl)benzenesulfonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrroio[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-3-ylethyl)benzenesulfonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-4-ylethyl)benzenesulfonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-3-yloxy)ethyl]benzenesulfonamide-   N-Benzyl4-(1,3-diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]benzenesuffonamide-   4-(2,4-Dioxo-1,3dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methyl-N-(2-pyridin-2-yl-ethyl)benzenesulfonamide-   4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylmethylbenzenesulfonamide-   4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-3-ylmethylbenzenesulfonamide-   N-(6-Methoxypyridin-3-ylmethyl)-4-(1-methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulfonamide-   N-Methyl-4-(1-methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulfonamide-   4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-3-ylethyl)benzenesulfonamide-   4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-4-ylethyl)benzenesulfonamide-   4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]benzenesulfonamide-   N-Benzyl-4-(1-methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]benzenesulfonamide-   4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro    1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylmethylbenzenesulfonamide-   4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro1H-pyrrolo[3,2-d]pynmidin-6-yl)-N-pyridin-3-ylmethylbenzenesulfonamide-   4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-4-ylmethylbenzenesulfonamide-   N-(6-Methoxypyridin-3-ylmethyl)-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulfonamide-   N-(3-Chloropyridin-4-ylmethyl)-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulfonamide-   N-Methyl-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulfonamide-   4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-3yl-ethyl)benzenesulfonamide-   4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-4-ylethyl)benzenesulfonamide-   4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)-ethyl]benzenesulfonamide-   1,3-Dimethyl-6-[4-(2,3,5,6-tetrahydro-[1,2]bipyrazinyl-4-sulfonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-(1-Ethyl-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylmethyl-benzenesulfonamide-   4-(1-Ethyl-3methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)-benzenesulfonamide-   4-(1-Ethyl-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrnmidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]-benzenesulfonamide-   4-(1-Ethyl-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxy-pyridin-3-ylmethyl)-benzenesulfonamide-   4-[1,3-Bis-(3-methoxypropyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]-N-pyridin-3-ylmethylbenzenesulphonamide-   6-{4-[4-(4Bromobenzyl)-piperazine-1-sulphonyl]phenyl}-1,3-bis-(2-methoxyethyl)-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-[1,3-Bis-(2-methylsulphanylethyl)-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]-N-pyrdin-4-ylmethylbenzenesulphonamide-   6-{4-[4-(4-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-bis-(2-methylsulphanyl-ethyl)-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   {4-[4-(4-Bromobenzyl)-piperazine-1-sulphonyl]phenyl}-3-methyl-1-pyridin-4-ylmethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione-   N-Methyl-4-(3-methyl-2,4-dioxo-1-pyridin-4-ylmethyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrmidin-6-yl)-N-(2-pyridin-2-yl-ethyl)benzenesulphonamide-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-3-methyl-1-phenethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione-   4-(Methy-l2,4-dioxo-1-phenethyl-2,3,4,5-tetrahydro1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylmethylbenzenesulphonamide-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-bis-cyclopropylmethyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4dione-   4-(1,3-Bis-cyclopropylmethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-3-yl-ethyl)benzenesulphonamide-   4-[2,4-Dioxo-1,3-bis-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]-N-(6-methoxypyridin-3-ylmethyl)benzenesulphonamide-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-bis-(2,2,2-trifluoroethyl)-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione-   N-(6-Methoxypyrdin-3-ylmethyl)-4-[3-methyl-1-(2-morpholin-4-yl-ethyl)-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]benzenesulphonamide-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-3-methyl-1-(2-morpholin-4-ylethyl)-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1-Benzyl-6-{4-[4-(4-bromobenzyl)piperazine-1-sulphonyl]phenyl}-3-methyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-(1-Benzyl-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]benzenesulphonamide-   3-{6-[4-(4-Benzylpiperazine-1-sulphonyl)pheny]-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro-pyrrolo[3,2-d]pyrimidin-1-yl}propionic    acid methyl ester-   4-[1-(3-Hydroxypropyl)-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]-N-[2-(pyridin-2-yloxy)ethyl]benzenesulphonamide-   3-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1-cyclopentyl-3-methyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-(1-Cyclopentyl-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-4-yl-ethyl)benzenesulphonamide

Of outstanding interest are:

-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]benzenesulfonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(6-methoxypyridin-2-yloxy)ethyl]benzenesulfonamide-   6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(4-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(3-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   1-Methyl-3-propyl-6-[4-(4-pyridin-2-ylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide-   4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylbenzenesulphonamide-   4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-yl)benzenesulphonamide-   6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione-   N-(1-Benzylpiperidin-4-yl)-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide-   4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(4-fluorobenzyl)piperidin-4-yl]benzenesulphonamide

According to a further feature of the present invention, the4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of generalformula (I) are prepared by reaction of the corresponding sulphonylchloride of formula (II):

(wherein R¹, R² and R³ are as hereinbefore defined) and thecorresponding amine (III):

(wherein R⁴ and R⁵ are as hereinbefore defined). The reaction is carriedout in an organic solvent, preferably a polar aprotic organic solventsuch as dioxane, methylene chloride or tetrahydrofuran, at a temperaturefrom 10° C. to 40° C. and in the presence of an organic base, preferablyan amine base such as triethylamine or polymer supported morpholine. Thethus obtained 4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivative isthen isolated by standard methods known in the art.

When R³ is hydrogen, the sulphonyl chloride of formula (II) is obtainedfrom the corresponding compound of formula (IV):

(wherein R¹, R² and R³ are as hereinbefore defined), by reaction with anexcess of chlorosulphonic acid and optionally thionyl chloride,preferably under a nitrogen atmosphere and at a temperature from −5° C.to 10° C.

When R³ is a chlorine atom, the sulphonyl chloride of formula (II) isobtained from the corresponding compound of formula (IV) by reactionwith a mixture of chlorosulphonic acid and sulphuryl chloride,preferably under a nitrogen atmosphere and at a temperature from −5° C.to 10° C.

When R³ is a bromine or an iodine atom, the sulphonyl chloride offormula (II) is obtained from the corresponding sulphonyl chloride offormula (II) where R³ is a hydrogen atom by reaction with bromine oriodine monochloride in glacial acetic acid at room temperature.

Other substitutions at R³ can be introduced by - reaction of thecorresponding compounds of the general formulae (II) or (IV), or aprotected version of them, with an appropiate electrophile.

The 6-phenyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione derivativesof formula (IV) can be prepared by reaction of the corresponding6-methyl-5-nitrouracils (V):

(wherein R¹ and R² are as hereinbefore defined), and benzaldehyde (VI):

followed by reductive cyclisation of the resulting5-nitro-6-styryluracils by methods known in the art, e.g. C. E. Mller etal., J. Med. Chem. 1994, 37, 1526-1534 and references cited therein.

When the defined groups R¹ to R⁵ are susceptible to chemical reactionunder the conditions of the hereinbefore described processes or areincompatible with said processes, alternative processes can be readilycarried out utllising organic synthetic chemistry methods to, forexample, protect functional groups and finally eliminate protectinggroups.

The 4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of formula(I) can be converted by methods known per se into pharmaceuticallyacceptable salts or N-oxides.

Preferred salts are acid addition salts obtainable by treatment withorganic or inorganic acids such as fumaric, tartaric, succinic orhydrochloric acid. Also 4-(pyrrolopyrimidin-6-yl)benzenesulphonamidederivatives of formula (I) in which there is the presence of an acidicgroup may be converted into pharmacologically acceptable salts byreaction with an alkali metal hydroxide or an organic base such assodium or potassium hydroxide. The acid or alkali addition salts soformed may be interchanged with suitable pharmaceutically acceptablecounter ions using processes known per se.

Adenosine 2B Receptor Subtype Competition Radioligand Binding

Human membranes from recombinant A_(2B) receptors were purchased fromReceptor Biology, Inc.(USA).

Competition assays were carried out by incubation of membranes fromhA_(2B) receptors transfected to HEK293 cells, [³H]DPCPX as radioligand,buffer (50 mM Tris-HCl (pH 6.5), 10 mM MgCl₂, 1 mM EDTA, 0.1 mMbenzamidine, 2 units/ml adenosine deaminase), and unlabelled ligand in atotal volume of 0.1 ml for 30 min at 25° C. NECA was used to determinatenon-specific binding. Filter over Schleicher&Schuell GF/52 filters(pre-soaked 0.5% polyethylenyimine) in a Brandel cell harvester. Unboundradioligand was removed with 4×2 ml ice-cold 50 mM Tris-Hcl (pH 6.5).

Adenosine 2A Receptor Subtype Competition Radioligand Binding

Human membranes from recombinant A_(2A) receptors were purchased fromReceptor Biology, Inc. (USA).

Competition assays were carried out by incubation of membranes fromhA_(2A) receptors transfected to HEK293 cells, [³H]ZM241385 asradioligand, buffer (50 mM Tris-HCl (pH 7.4), 10 mM MgCl₂, 1 mM EDTA, 2units/ml adenosine deaminase), and unlabelled ligand in a total volumeof 0.2 ml for 90 min at 25° C. NECA was used to determinate non-specificbinding. Filter over Schleicher&Schuell GF/52 filters (pre-soaked 0.5%polyethylenyimine) in a Brandel cell harvester. Unbound radioligand wasremoved with 3×3 ml ice-cold 50 mM Tris-Hcl 50 (pH 7.4), 0.9% NaCl.

The results are shown in Table 1 and Table 2.

TABLE 1 Example IC₅₀ A_(2B) (nM) 172 17 173 5 1 16 107 9 118 6 3 7 12612 37 14 132 17 38 12 36 18 18 4

It can be seen from Table 1 that the compounds of formula (I) are potentinhibitors of the A_(2B) adensosine receptor subtype. Preferred4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of theinvention possess an IC₅₀ value for the inhibition of A_(2B) (determinedas defined above) of less than 50 nM, preferably less than 20 nM andmost preferably less than 10 nM.

TABLE 2 Example IC₅₀ A_(2A) (nM) 18 85 59 28 38 75 97 60 69 84

It can be seen from Table 2 that the compounds of formula (I) are potentinhibitors of the A_(2A) adenosine receptor subtype. Some preferred4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of theinvention possess an IC₅₀ value for the inhibition of A_(2A) (determinedas defined above) of less than 100 nM and most preferably less than 50nM.

The 4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of theinvention are useful in the treatment or prevention of diseases known tobe susceptible to improvement by treatment with an antagonist of A_(2A)and/or A_(2B) adenosine receptors. For example (see WO 01/16134, WO01/02400, WO 01/80893 or WO 00/73307), Parkinson's disease, Alzheimer'sdisease, Huntington chorea, Wilson's disease, asthma,bronchoconstriction. allergic diseases. inflammation, reperfusioninjury, myocardial ischemia, atherosclerosis, hypertension, retinopathy,diabetes mellitus, inflammation, gastrointestinal tract disorders,and/or autoimmune diseases. Examples of autoimmune diseases which can betreated or prevented using the compounds of the invention are Addison'sdisease, autoimmune hemolytic anemia, Crohn's disease, Goodpasture'ssyndrome, Graves disease, Hashimoto's thyrolditis, idiopathicthrombocytopenic purpura, insulin-dependent diabetes mellitus, multiplesclerosis, myasthenia gravis, pemphigus vulgaris, pernicious anemia,poststreptococcal glomerulonephritis, psoriasis, rheumatoid arthritis,scleroderma, Sjogren's syndrome, spontaneous infertility, and systemiclupus erythematosus.

Accordingly, the 4-(pyrrolopyrimidinyl)benzenesulphonamide derivativesof the invention and pharmaceutically acceptable salts thereof, andpharmaceutical compositions comprising such compound and/or saltsthereof, may be used in a method of treatment of disorders of the humanbody which comprises administering to a subject requiring such treatmentan effective amount of a 4-(pyrrolopyrimidin-6-yl)benzenesulphonamidederivative of the invention or a pharmaceutically acceptable saltthereof.

The present invention also provides pharmaceutical compositions whichcomprise, as an active ingredient, at least a4-(pyrrolopyrimidin6-yl)benzenesulphonamide derivative of formula (I) ora pharmaceutically acceptable salt thereof in association with apharmaceutically acceptable excipient such as a carrier or diluent. Theactive ingredient may comprise 0.001% to 99% by weight, preferably 0.01%to 90% by weight of the composition depending upon the nature of theformulation and whether further dilution is to be made prior toapplication. Preferably the compositions are made up in a form suitablefor oral, topical, nasal, rectal, percutaneous or injectableadministration.

The pharmaceutically acceptable excipients which are admixed with theactive compound, or salts of such compound, to form the compositions ofthis invention are well-known per se and the actual excipients useddepend inter alia on the intended method of administering thecompositions.

Compositions of this invention are preferably adapted for injectable andper os administration. In this case, the compositions for oraladministration may take the form of tablets, retard tablets, sublingualtablets, capsules, inhalation aerosols, inhalation solutions, dry powderinhalation, or liquid preparations, such as mixtures, elixirs, syrups orsuspensions, all containing the compound of the invention; suchpreparations may be made by methods well-known in the art.

The diluents which may be used in the preparation of the compositionsinclude those liquid and solid diluents which are compatible with theactive ingredient, together with colouring or flavouring agents, ifdesired. Tablets or capsules may conveniently contain between 2 and 500mg of active ingredient or the equivalent amount of a salt thereof.

The liquid composition adapted for oral use may be in the form ofsolutions or suspensions. The solutions may be aqueous solutions of asoluble salt or other derivative of the active compound in associationwith, for example, sucrose to form a syrup. The suspensions may comprisean insoluble active compound of the invention or a pharmaceuticallyacceptable salt thereof in association with water, together with asuspending agent or flavouring agent.

Compositions for parenteral injection may be prepared from solublesalts, which may or may not be freeze-dried and which may be dissolvedin pyrogen free aqueous media or other appropriate parenteral injectionfluid.

Effective doses are normally in the range of 2-2000 mg of activeingredient per day. Daily dosage may be administered in one or moretreatments, preferably from 1 to 4 treatments, per day.

The syntheses of the compounds of the invention and of the intermediatesfor use therein are illustrated by the following Examples (includingPreparation Examples (Preparations 1-12)) which do not limit the scopeof the invention in any way.

¹H Nuclear Magnetic Resonance Spectra were recorded on a Varian Gemini300 spectrometer. Melting points were recorded using a Perkin ElmerDSC-7 apparatus. The chromatographic separations were obtained using aWaters 2690 system equipped with a Symmetry C18 (2.1×10 mm, 3.5 μM)column. As detectors a Micromass ZMD mass spectrometer using ESionization and a Waters 996 Diode Array detector were used. The mobilephase was formic acid (0.46 ml), ammonia (0.115 ml) and water (1000 ml)(A) and formic acid (0.4 ml), ammonia (0.1 ml), methanol (500 ml) andacetonitrile (500 ml) (B): initially from 0% to 95% of B in 20 min. andthen 4 min. with 95% of B. The reequilibration time between twNoinjections was 5 min. The flow rate was 0.4 ml/min. The injection volumewas 5 μl. Diode array chromatograms were processed at 210 nm.

PREPARATION EXAMPLES Preparation 14-(1,3-Dimethyl-2,4-dioxo-2,3,4,5tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-benzenesulphonylchloride

a) A mixture of 1,3,6-trimethyl-5-nitro-1H-pyrimidine-2,4dione (3.00 g,15.06 mmol), benzaldehyde (1.58 ml, 15.56 mmol), piperidine (1.41 ml,15.56 mmol) and a 3 Å molecular sieve (6.00 g) in ethanol (70 ml) wasrefluxed for 4 hours, filtered and the solid was treated with a mixtureof chloroform and methanol. The resulting suspension was filtered againand the filtrates were evaporated. The residue was triturated withdiethyl ether and the precipitate collected by filtration and driedunder vacuum to yield1,3-dimethyl-5-nitro-6-((E)styryl)-1H-pyrimidine-2,4-dione (2.61 g, 60%)as a yellow solid.

b) To a stirred solution of the above compound (2.61 g, 9.08 mmol) informic acid (80 ml) was slowly added sodium dithionite (9.30 g, 45.42mmol) and the mixture was refluxed overnight. The resulting mixture wascooled to room temperature and it was poured into water. The precipitatewas collected by filtration, washed with water and dichloromethane andthen dried under vacuum to yield1,3dimethyl-6-phenyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione (1.54g, 66%) as a white solid.

c) The above compound (500 mg, 1.96 mmol) was added portionwise to amixture of chlorosulphonic acid (2.5 ml) and thionyl chloride (0.25 ml)and stirred at 0° C. for 1 hour and then at room temperature for 1 h 30min. The reaction mixture was carefully poured into stirred ice-waterand the resulting precipitate was collected by filtration, washed withwater and diethyl ether and then dried under vacuum to yield the titleproduct (607 mg, 88%) as a yellow solid.

¹H-NMR δ(DMSO): 12.5 (s, 1H), 7.9 (d, 2H), 7.6 (d, 2H), 6.8 (s, 1H), 3.5(s, 3H), 3.3 (s, 3H).

Preparation 24-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

Obtained as a yellow solid (29% overall) from1,3-diethyl-6-methyl-5-nitro-1H-pyrimidine-2,4-dione following theprocedure described in Preparation 1.

¹H-NMR δ(DMSO): 12.4 (s, 1H), 7.9 (d, 2H), 7.8 (d, 2H), 6.8 (s, 1H), 3.9(m, 4H), 1.2 (dt, 6H).

Preparation 34-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

Obtained as a yellow solid (18% overall) from6-methyl-5-nitro-1,3-diprbpyl-1H-pyrimidine-2,4-dione following theprocedure described in Preparation 1.

¹H-NMR δ(DMSO): 12.2 (s, 1H), 7.9 (d, 2H), 7.6 (d, 2H), 6.8 (s, 1H), 3.9(m, 4H), 1.6 (m, 4H), 0.9 (m, 6H).

Preparation 44-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

Obtained as a yellow solid (50% overall) from1,6-dimethyl-5-nitro-3-propyl-1H-pyrimidine-2,4-dione following theprocedure described in Preparation 1.

¹H-NMR δ(DMSO): 12.4 (s, 1H), 7.9 (d, 2H), 7.6 (d, 2H), 6.65 (s, 1H),3.9 (t, 2H), 3.4 (s, 3H), 1.6 (m, 2H), 0.9 (t, 3H).

Preparation 54-(3Methyl-2,4-dioxo-1-propyl-2,3,4,5tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

Obtained as a yellow solid (40% overall) from3,6-dimethyl-5-nitro-1-propyl-1H-pyrimidine-2,4-dione following theprocedure described in Preparation 1.

¹H-NMR δ(DMSO): 12.4 (s, 1H), 7.9 (d, 2H), 7.6 (d, 2H), 5.8 (s,1H), 3.85(t, 2H), 3.35 (s, 3H), 1.7 (m, 2H), 0.9 (t, 3H).

Preparation 6

4-(7-Chloro-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

The title compound of Preparation 1 (600 mg,1.69 mmol) was suspended inglacial acetic acid (6 ml), sulphuryl chloride was added dropwise (205μl, 2.54 mmol) and the mixture was stirred at room temperature for 3hours. The reaction mixture was then filtered, washed with dietyhl etherand dried to yield the title product as a yellow solid (384 mg, 58%).

¹H-NMR δ(DMSO): 12.9 (s, 1H), 7.6 (m, 4H), 3.7 (s, 3H), 3.2 (s, 3H).

EXAMPLES

TABLE 3 (I)

R¹R² R¹ = Me R¹ = Et R¹ = nPro R¹ = nPro R¹ = Me R² = Me R² = Et R² =nPro R² = Me R² = nPro NR⁴R⁵ Compounds of formula (I) wherein R³ = H:  143 76 106 133

 2 44 77 107 134

 3 45 78 108 135

 4 46 79 109 —

 5 — — — —

 6 47 80 110 136

 7 48 81 111 137

 8 49 82 112 138

 9 50 83 113 139

 10 51 84 114 140

 11 52 85 115 141

 12 53 86 116 142

 13 54 87 117 143

 14 55 88 118 144

 15 56 89 119 145

 16 57 — 120 —

 17 58 90 121 146

 18 59 91 122 147

 19 60 92 123 148

 20 61 93 — 149

 21 — — — 150

 22 62 94 124 151

— 63 95 — 152

 23 — — — —

 24 64 — — 153

 25 — — — —

 26 65 — 125 154

— 66 — — 155

 27 67 96 126 156

 28 — — — —

 29 68 97 127 157

 30 69 98 128 158

 31 70 99 129 159

 32 71 100  130 160

 33 72 101  131 161

 34 73 102  — —

 35 74 — — —

 36 — 103  — —

 37 75 104  132 162

 38 — 105  — —

 39 — — — —

 40 — — — —

 41 — — — —

 42 — — — —

164 186  — 196 204

165 187  — 197 205

166 188  — — 206

167 189  — 198 207

168 — — 208

169 190  195  199 209

170 191  — 200 210

171 192  — 201 211

172 193  — 202 212

173 — — — —

174 — — — —

175 — — — —

176 — — — —

177 — — — —

178 — — — —

179 — — — —

180 — — — —

181 194  — −203

182 — — — —

183 — — — —

184 — — — —

185 — — — —

Compounds of formula (I) wherein R³ = Cl: 163 — — — —

Example 16-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

To a mixture of the title compound of Preparation 1 (0.1 g, 0.28 mmol)and triethylamine (0.043 ml, 0.31 mmol) in dichloromethane (5 ml) wasadded 1-benzylpiperazine (0.054 ml, 0.31 mmol) and the resulting mixturewas stirred at room temperature overnight. The reaction mixture wasdiluted with dichloromethene, washed with an aqueous solution of sodiumbicarbonate in water, dried (MgSO₄) and evaporated under reducedpressure. The resulting crude residue was triturated with diethyletherand the precipitate collected by filtration and dried under vacuum toyield the title compound (65 mg, 47%).

ESI/MS m/e: 494 ([M+H]⁺, C₂₅H₂₇N₅O₄S) Retention Time (min.): 6.6

Examples 2-42 and 164-185

These compounds were synthesized from the title compound of Preparation1 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummarised in Table 4.

TABLE 4 ESI/MS m/e Retention Example Molecular Formula [M + H]⁺ Time(min.) Yield % 2 C₂₅H₂₆FN₅O₄S 512 6.5 52 3 C₂₅H₂₆FN₅O₄S 512 7.2 35 4C₂₅H₂₅F₂N₅O₄S 530 7.5 44 5 C₂₅H₂₆FN₅O₄S 512 6.9 85 6 C₂₅H₂₆ClN₅O₄S 5287.4 70 7 C₂₅H₂₆ClN₅O₄S 528 7.9 70 8 C₂₅H₂₆BrN₅O₄S 572 7.7 50 9C₂₅H₂₆BrN₅O₄S 573 8.8 56 10 C₂₆H₂₆F₃N₅O₄S 562 8.6 74 11 C₂₉H₃₅N₅O₄S 5508.0 35 12 C₂₆H₂₉N₅O₅S 524 5.9 65 13 C₂₆H₂₉N₅O₅S 524 6.3 62 14C₂₆H₂₇N₅O₆S 538 6.5 58 15 C₂₆H₂₆N₆O₄S 519 7.2 58 16 C₂₃H₂₅N₅O₅S 484 5.529 17 C₂₃H₂₅N₅O₄S₂ 500 6.6 80 18 C₂₃H₂₄ClN₅O₄S₂ 535 8.9 84 19C₂₄H₂₆N₆O₄S 495 5.8 26 20 C₂₆H₂₉N₅O₄S 508 6.2 50 21 C₂₆H₂₉N₅O₄S 508 5.854 22 C₂₆H₂₈FN₅O₄S 526 6.3 59 23 C₂₇H₂₉N₅O₄S 520 6.5 58 24 C₂₆H₂₇N₅O₄S506 5.6 64 25 C₃₁H₃₁N₅O₄S 570 10.7 66 26 C₂₄H₂₇N₅O₄S 482 5.9 62 27C₂₃H₂₄N₆O₄S 481 7.1 58 28 C₂₃H₂₅N₇O₅S 512 6.6 63 29 C₂₆H₂₉N₅O₄S 508 5.844 30 C₂₆H₂₈FN₅O₄S 526 5.9 60 31 C₂₈H₃₃N₅O₆S 566 5.4 49 32 C₂₄H₂₇N₅O₄S₂514 5.3 54 33 C₂₇H₃₁N₅O₄S 522 6.0 47 34 C₂₅H₂₇N₅O₄S 494 5.5 72 35C₂₆H₂₉N₅O₄S 508 5.7 74 36 C₂₀H₁₉N₅O₅S 442 8.0 84 37 C₂₁H₂₁N₅O₄S 440 5.554 38 C₁₉H₁₇N₅O₄S 412 6.6 52 39 C₂₀H₁₉N₅O₄S 526 6.4 24 40 C₂₄H₂₅N₅O₄S480 9.4 81 41 C₂₅H₂₄F₃N₅O₄S 548 10.2 26 42 C₂₃H₂₂Cl₂N₆O₄S 550 9.5 48 164C₂₀H₁₉N₅O₄S 426 6.4 45 165 C₂₀H₁₉N₅O₄S 426 5.7 82 166 C₂₀H₁₉N₅O₄S 4265.3 44 167 C₂₁H₂₁N₅O₅S 456 7.2 52 168 C₂₀H₁₈ClN₅O₄S 461 7.3 25 169C₂₂H₂₃N₅O₄S 455 6.0 15 170 C₂₁H₂₁N₅O₄S 440 5.4 58 171 C₂₁H₂₁N₅O₄S 4405.1 65 172 C₂₁H₂₁N₅O₅S 456 7.3 66 173 C₂₂H₂₃N₅O₆S 487 8.1 89 174C₂₂H₂₃N₅O₅S 471 7.6 90 175 C₂₁H₂₀ClN₅O₅S 491 8.3 91 176 C₂₂H₂₀F₃N₅O₅S524 8.5 65 177 C₂₁H₂₁N₅O₅S 456 5.8 85 178 C₂₀H₂₀N₆O₅S 457 6.9 68 179C₂₁H₂₁N₅O₄S₂ 473 7.8 75 180 C₂₀H₂₀N₆O₄S₂ 474 7.1 65 181 C₂₈H₂₇N₅O₅S 5479.3 44 182 C₂₉H₂₉N₅O₆S 577 10.1 74 183 C₂₈H₂₆ClN₅O₅S 581 9.4 74 184C₂₆H₂₈N₄O₄S 494 9.8 54 185 C₂₆H₂₈N₄O₅S 510 9.3 49

Example 172

δ ¹H NMR (DMSO): 12.65 (bs, 1H), 8.18 (d, 2H), 7.95 (t, 1H), 7.82 (d,2H), 7.66 (dd, 1H), 6.98 (t, 1H), 6.9 (s, 1H), 6.75 (d, 1H), 4.22 (t,2H), 3.43 (s, 3H), 3.25 (s, 3H), 3.21 (q, 2H).

Example 173

δ ¹H NMR (DMSO): 8.05 (d, 2H), 7.85 (d, 2H), 7.50 (t, 1H), 6.90 (s, 1H),6.25 (t, 2H), 4.20 (m, 2H), 3.80 (s, 3H), 3.45 (s, 3H), 3.35 (m, 2H),3.15 (s, 3H), 3.05 (s, 3H).

Examples 43-75 and 186-194

These compounds were synthesized from the title oompound of Preparation2 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummrarised in Table 5.

TABLE 5 ESI/MS m/e Retention Example Molecular Formula [M + H]⁺ Time(min.) Yield % 43 C₂₇H₃₁N₅O₄S 522 7.1 20 44 C₂₇H₃₀FN₅O₄S 540 7.5 70 45C₂₇H₃₀FN₅O₄S 540 8.3 62 46 C₂₇H₂₉F₂N₅O₄S 558 8.6 65 47 C₂₇H₃₀ClN₅O₄S 5568.6 48 48 C₂₇H₃₀ClN₅O₄S 556 9.1 77 49 C₂₇H₃₀BrN₅O₄S 601 8.9 76 50C₂₇H₃₀BrN₅O₄S 601 9.9 63 51 C₂₈H₃₀F₃N₅O₄S 590 9.6 60 52 C₃₁H₃₉N₅O₄S 5788.9 58 53 C₂₈H₃₃N₅O₅S 552 6.7 70 54 C₂₈H₃₃N₅O₅S 552 7.2 36 55C₂₈H₃₁N₅O₆S 566 6.9 44 56 C₂₈H₃₀N₆O₄S 547 8.3 50 57 C₂₅H₂₉N₅O₅S 512 6.350 58 C₂₅H₂₉N₅O₄S₂ 528 7.7 66 59 C₂₅H₂₈ClN₅O₄S₂ 562 9.8 74 60C₂₆H₃₀N₆O₄S 523 6.7 39 61 C₂₈H₃₃N₅O₄S 536 7.0 28 62 C₂₈H₃₂N₅O₄S 554 6.680 63 C₂₈H₃₃N₅O₄S 536 6.8 62 64 C₂₈H₃₁N₅O₄S 534 6.2 57 65 C₂₆H₃₁N₅O₄S510 6.2 47 66 C₂₇H₃₃N₅O₅S 540 6.2 60 67 C₂₅H₂₈N₆O₄S 509 7.8 56 68C₂₈H₃₃N₅O₄S 536 6.1 70 69 C₂₈H₃₂FN₅O₄S 554 6.2 63 70 C₃₀H₃₇N₅O₆S 596 6.051 71 C₂₆H₃₁N₅O₄S₂ 542 6.0 74 72 C₂₉H₃₅N₅O₄S 550 6.3 38 73 C₂₇H₃₁N₅O₄S522 6.0 32 74 C₂₈H₃₃N₅O₄S 536 6.3 87 75 C₂₃H₂₅N₅O₄S 468 6.5 36 186C₂₂H₂₃N₅O₄S 455 7.4 54 187 C₂₂H₂₃N₅O₄S 455 6.7 86 188 C₂₂H₂₃N₅O₄S 4556.2 85 189 C₂₃H₂₅N₅O₅S 485 8.1 75 190 C₂₄H₂₇N₅O₄S 483 7.0 74 191C₂₃H₂₅N₅O₄S 469 6.3 61 192 C₂₃H₂₅N₅O₄S 469 6.0 80 193 C₂₃H₂₅N₅O₅S 4858.2 58 194 C₃₀H₃₁N₅O₅S 575 9.9 65

Examples 76-105 and 195

These compounds were synthesized from the title compound of Preparation3 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummarised in Table 6.

TABLE 6 ESI/MS m/e Retention Example Molecular Formula [M + H]⁺ Time(min.) Yield % 76 C₂₉H₃₅N₅O₄S 550 8.4 60 77 C₂₉H₃₄FN₅O₄S 568 8.7 74 78C₂₉H₃₄FN₅O₄S 568 9.5 90 79 C₂₉H₃₃F₂N₅O₄S 586 9.7 58 80 C₂₉H₃₄ClN₅O₄S 5869.9 57 81 C₂₉H₃₄ClN₅O₄S 585 10.2 39 82 C₂₉H₃₄BrN₅O₄S 629 10.1 58 83C₂₉H₃₄BrN₅O₄S 629 10.8 64 84 C₃₀H₃₄F₃N₅O₄S 618 10.5 68 85 C₃₃H₄₃N₅O₄S606 10.1 75 86 C₃₀H₃₇N₅O₅S 580 7.7 49 87 C₃₀H₃₇N₅O₅S 580 8.4 31 88C₃₀H₃₅N₅O₆S 594 7.9 54 89 C₃₀H₃₄N₆O₄S 575 9.4 52 90 C₂₇H₃₃N₅O₄S₂ 556 9.061 91 C₂₇H₃₂ClN₅O₄S₂ 592 10.6 25 92 C₂₈H₃₄N₆O₄S 551 7.9 74 93C₃₀H₃₇N₅O₄S 564 8.2 52 94 C₃₀H₃₆FN₅O₄S 582 7.4 70 95 C₃₀H₃₇N₅O₄S 564 7.869 96 C₂₇H₃₂N₆O₄S 537 9.0 33 97 C₃₀H₃₇N₅O₄S 564 6.9 30 98 C₃₀H₃₆FN₅O₄S582 6.9 55 99 C₃₂H₄₁N₅O₆S 624 6.8 80 100 C₂₈H₃₅N₅O₄S₂ 570 6.7 77 101C₃₁H₃₉N₅O₄S 578 7.1 29 102 C₂₉H₃₅N₅O₄S 550 6.8 38 103 C₂₄H₂₇N₅O₅S 4989.2 49 104 C₂₅H₂₉N₅O₄S 496 7.8 54 105 C₂₃H₂₅N₅O₄S 468 8.1 66 195C₂₆H₃₁N₅O₄S 511 8.4 71

Examples 106-132 and 196-203

These compounds were synthesized from the title compound of Preparation4 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummarised in Table 7.

TABLE 7 ESI/MS m/e Retention Example Molecular Formula [M + H]⁺ Time(min.) Yield % 106 C₂₇H₃₁N₅O₄S 522 7.2 70 107 C₂₇H₃₀FN₅O₄S 540 7.6 66108 C₂₇H₃₀FN₅O₄S 540 8.2 29 109 C₂₇H₂₉F₂N₅O₄S 558 8.5 27 110C₂₇H₃₀ClN₅O₄S 557 8.6 35 111 C₂₇H₃₀ClN₅O₄S 556 9.2 57 112 C₂₇H₃₀BrN₅O₄S601 8.9 84 113 C₂₇H₃₀BrN₅O₄S 601 9.9 48 114 C₂₈H₃₀F₃N₅O₄S 590 9.6 41 115C₃₁H₃₉N₅O₄S 578 8.9 32 116 C₂₈H₃₃N₅O₅S 552 6.7 58 117 C₂₈H₃₃N₅O₅S 5527.3 51 118 C₂₈H₃₁N₅O₆S 566 6.9 55 119 C₂₈H₃₀N₆O₄S 547 8.3 64 120C₂₅H₂₉N₅O₅S 512 6.3 35 121 C₂₅H₂₉N₅O₄S₂ 528 7.7 48 122 C₂₅H₂₈ClN₅O₄S₂563 9.8 54 123 C₂₆H₃₀N₆O₄S 523 6.7 59 124 C₂₈H₃₂FN₅O₄S 554 6.6 65 125C₂₆H₃₁N₅O₄S 510 6.3 80 126 C₂₅H₂₈N₆O₄S 509 7.8 47 127 C₂₈H₃₃N₅O₄S 5366.1 81 128 C₂₈H₃₂FN₅O₄S 554 6.3 56 129 C₃₀H₃₇N₅O₆S 596 6.1 63 130C₂₆H₃₁N₅O₄S₂ 542 6.1 65 131 C₂₉H₃₅N₅O₄S 550 6.4 68 132 C₂₃H₂₅N₅O₄S 4686.6 64 196 C₂₂H₂₃N₅O₄S 455 7.4 85 197 C₂₂H₂₃N₅O₄S 455 6.8 84 198C₂₃H₂₅N₅O₅S 485 8.1 66 199 C₂₄H₂₇N₅O₄S 483 7.1 91 200 C₂₃H₂₅N₅O₄S 4696.4 45 201 C₂₃H₂₅N₅O₄S 469 6.0 30 202 C₂₃H₂₅N₅O₅S 485 8.2 57 203C₃₀H₃₁N₅O₅S 575 10.0 66

Examples 133-162 and 204-212

These compounds were synthesized from the title compound of Preparation5 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummarised in Table 8.

TABLE 8 ESI/MS m/e Retention Example Molecular Formula [M + H]⁺ Time(min.) Yield % 133 C₂₇H₃₁N₅O₄S 522 7.3 45 134 C₂₇H₃₀FN₅O₄S 540 7.5 49135 C₂₇H₃₀FN₅O₄S 540 8.5 58 136 C₂₇H₃₀ClN₅O₄S 556 8.8 84 137C₂₇H₃₀ClN₅O₄S 556 9.3 29 138 C₂₇H₃₀BrN₅O₄S 601 9.0 28 139 C₂₇H₃₀BrN₅O₄S601 10.0 56 140 C₂₈H₃₀F₃N₅O₄S 590 9.7 45 141 C₃₁H₃₉N₅O₄S 578 9.1 54 142C₂₈H₃₃N₅O₅S 552 6.8 48 143 C₂₈H₃₃N₅O₅S 552 7.4 50 144 C₂₈H₃₁N₅O₆S 5667.1 72 145 C₂₈H₃₀N₆O₄S 547 8.4 77 146 C₂₅H₂₉N₅O₄S₂ 528 7.8 66 147C₂₅H₂₈ClN₅O₄S₂ 562 9.8 36 148 C₂₆H₃₀N₅O₄S 523 6.8 39 149 C₂₈H₃₃N₅O₄S 5367.1 47 150 C₂₈H₃₃N₅O₄S 536 6.5 78 151 C₂₈H₃₂FN₅O₄S 554 6.7 59 152C₂₈H₃₃N₅O₄S 536 6.9 66 153 C₂₈H₃₁N₅O₄S 534 6.3 60 154 C₂₈H₃₁N₅O₄S 5106.3 69 155 C₂₇H₃₃N₅O₅S 540 6.3 49 156 C₂₅H₂₈N₈O₄S 509 7.8 75 157C₂₈H₃₃N₅O₄S 536 6.2 38 158 C₂₈H₃₂FN₅O₄S 554 6.2 24 159 C₃₀H₃₇N₅O₆S 5966.0 62 160 C₂₈H₃₁N₅O₄S₂ 542 6.0 50 161 C₂₉H₃₅N₅O₄S 550 6.4 47 162C₂₃H₂₅N₅O₄S 468 6.6 58 204 C₂₂H₂₃N₅O₄S 455 7.5 45 205 C₂₂H₂₃N₅O₄S 4556.9 58 206 C₂₂H₂₃N₅O₄S 455 6.4 91 207 C₂₃H₂₅N₅O₅S 485 8.2 75 208C₂₂H₂₂ClN₅O₄S 489 8.2 71 209 C₂₄H₂₇N₅O₄S 483 7.2 84 210 C₂₃H₂₅N₅O₄S 4696.4 58 211 C₂₃H₂₅N₅O₄S 469 6.0 66 212 C₂₃H₂₅N₅O₅S 485 8.3 62

Example 163

This compound was synthesized from the title compound of Preparation 6and from 1-benzylpiperazine following the procedure of example 1.

ESI/MS m/e: 529 ([M+H]⁺, C₂₅H₂₆ClN₅O₄S) Retention Time (min.): 7.4

The following examples illustrate pharmaceutical compositions accordingto the present invention and procedure for their preparation.

Composition Example 1

50,000 capsules each containing 100 mg of3-methyl-6-[5-(4-methylpiperazine-1-sulphonyl)-2-propoxyphenyl]-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione(active ingredient) were prepared according to the followingformulation:

Active ingredient 5 Kg Lactose monohydrate 10 Kg Colloidal silicondioxide 0.1 Kg Corn starch 1 Kg Magnesium stearate 0.2 Kg

Procedure

The above ingredients were sieved through a 60 mesh sieve, and wereloaded into a suitable mixer and filled into 50,000 gelatine capsules.

Composition Example 2

50,000 tablets each containing 50 mg of6-[5-(ethylpiperazine-1-sulphonyl)-2-propoxyphenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4dione(active ingredient) were prepared from the following formulation:

Active ingredient 2.5 Kg Microcrystalline cellulose 1.95 Kg Spray driedlactose 9.95 Kg Carboxymethyl starch 0.4 Kg Sodium stearyl fumarate 0.1Kg Colloidal silicon dioxide 0.1 Kg

Procedure

All the powders were passed through a screen with an aperture of 0.6 mm,then mixed in a suitable mixer for 20 minutes and compressed into 300 mgtablets using 9 mm disc. and flat bevelled punches. The disintegrationtime of the tablets was about 3 minutes.

1. A compound of formula (I)

wherein R¹ and R² each independently represents: a) a hydrogen atom; b)a hydrocarbon chain chosen from an alkyl, alkenyl and alkynyl groups,wherein said hydrocarbon chain is optionally substituted by one or moresubstituents chosen from halogen, hydroxy, alkoxy, alkylthio, amino,monoalkylamino, dialkylamino, cyano, oxo, hydroxycarbonyl,alkoxycarbonyl, acylamino, carbamoyl, alkylcarbamoyl,dihydroxyphosphoryloxy and dialkoxyphosphoryloxy groups; or c) a groupof formula—(CH₂)_(n)—R⁶ n is an integer from 0 to 4 and R⁶ represents a 3- to7-membered aromatic or non-aromatic cyclic group containing from 0 to 4heteroatoms chosen from N, O and S, wherein said 3- to 7-memberedaromatic or non-aromatic cyclic group is optionally bridged and/or fusedto another 3- to 7-membered aromatic or non-aromatic cyclic groupcontaining from 0 to 4 heteroatoms chosen from N, O and S; and whereineach of the cyclic groups in the moiety R⁶ being is independentlyoptionally substituted by one or more R⁷ substituents; R⁷ represents agroup chosen from halogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl,cycloalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, hydroxy,alkylenedioxy, alkoxy, alkylthio, amino, monoalkylamino, dialkylamino,nitro, cyano, oxo, hydroxycarbonyl, alkoxycarbonyl, acylamino,carbamoyl, alkylcarbamoyl, dihydroxyphosphoryloxy anddialkoxyphosphoryloxy groups; wherein each of the hydrocarbon chains andeach of the cyclic moieties in R⁷ is independently optionallysubstituted by one or more further R⁸ substituents, R⁸ represents agroup chosen from halogen, hydroxy, oxo, cyano, alkyl, difluoromethyl,trifluoromethyl, alkoxy, alkylenedioxy, alkylthio acylamino, carbamoyl,alkylcarbamoyl, dihydroxyphosphoryloxy, dialkoxyphosphoryloxy,hydroxyalkoxy, phenyl, alkoxycarbonyl, amino, monoalkylamino,dialkylamino and hydroxycarbonyl groups; R³ represents a hydrogen orhalogen atom, or a nitro, alkoxycarbonyl or alkyl group; wherein thealkyl group is optionally substituted by one or more substituents chosenfrom hydroxy, alkoxy, alkylthio, amino, monoalkylamino, dialkylamino,hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl sandalkylcarbamoyl groups; R⁴ and R⁵ are the same or different, eachindependently representing: a) hydrogen; b) a group of formula—(CH₂)_(n)—R⁶; c) or a hydrocarbon chain chosen from alkyl, alkenyl andalkynyl, wherein said hydrocarbon chain is optionally substituted by oneor more substituents chosen from —(CH₂)_(n)—R⁶, —O—(CH₂)_(n)—R⁶,—S—(CH₂)_(n)—R⁶, —NH—(CH₂)_(n)—R⁶, hydroxy, oxo, halogen, alkoxy,alkylthio, amino, monoalkylamino, and dialkylamino groups; wherein eachof the alkyl chains in the alkoxy, alkylthio, monoalkylamino ordialkylamino substituents is independently optionally substituted by oneor more further substituents chosen from —(CH₂)_(n)—R⁶, hydroxy, oxo,halogen, alkoxy, alkylthio, amino, monoalkylamino and dialkylaminogroups; wherein each n is independently an integer from 0 to 4 and eachR⁶ is independently chosen from each other; or d) alternatively, R⁴ andR⁵, together with the nitrogen atom to which they are attached, form a3- to 7-membered aromatic or non-aromatic cyclic group containing from 1to 4 heteroatoms chosen from N, O and S, wherein said 3- to 7-memberedaromatic or non-aromatic cyclic group is optionally bridged and/or fusedto another 3- to 7-membered aromatic or non-aromatic cyclic groupcontaining from 0 to 4 heteroatoms chosen from N, O and S; wherein eachof the cyclic groups is independently optionally substituted by one ormore substituents chosen from —(CH₂)_(n)R⁶ and R⁷; wherein each of thehydrocarbon chains and each of the cyclic moieties of the R⁷substituents is independently optionally substituted by one or morefurther substituents chosen from—(CH₂)_(n)—R⁶ and R⁸; wherein each ofthe alkyl chains in the R⁸ substituents is independently optionallysubstituted by one or more further substitutents chosen from—(CH₂)_(n)—R⁶, hydroxy, halogen, alkoxy, alkylthio, amino,monoalkylamino and dialkylamino groups; wherein each of the R⁶substituents is independently chosen from each other; or an N-oxide or apharmaceutically acceptable salt thereof.
 2. A compound according toclaim 1, wherein each of R¹ and R² independently represents: a) an alkylgroup optionally substituted by one or more substituents chosen fromhydroxy, halogen, alkoxy, alkylthio, amino, monoalkylamino,dialkylamino, hydroxycarbonyl, and alkoxycarbonyl groups; or b) a groupof formula —(CH₂)_(n)—R⁶, wherein n is an integer from 0 to 2 and R⁶represents a 3- to 7-membered aromatic or non-aromatic cyclic grouphaving from 0 to 2 heteroatoms chosen from nitrogen and oxygen.
 3. Acompound according to claim 2 wherein R¹ and R² are both unsubstitutedC₁-C₆ alkyl groups.
 4. A compound according to claim 1, wherein R³represents hydrogen or a halogen atom.
 5. A compound according to claim1, wherein R⁵ is hydrogen, a group of formula —(CH₂)_(n)R⁶ or ahydrocarbon chain chosen from alkyl, alkenyl and alkynyl, wherein saidhydrocarbon chain is optionally substituted by one or more groups chosenfrom —(CH₂)_(n)—R⁶ and —O—(CH₂)_(n)—R⁶; wherein each R⁶ is independentlya phenyl or a pyridyl group, and wherein each R⁶ is independentlyoptionally substituted by one or more substituents chosen from halogen,hydroxy, alkyl, alkoxy and alkylthio groups.
 6. A compound according toclaim 5, wherein R⁵ is hydrogen or an alkyl group.
 7. A compound offormula (I)

wherein R¹ and R² each independently represents: a) hydrogen atom; b)hydrocarbon chain chosen from an alkyl, alkenyl and alkynyl groups,wherein said hydrocarbon chain is optionally substituted by one or moresubstituents chosen from halogen, hydroxy, alkoxy, alkylthio, amino,monoalkylamino, dialkylamino, cyano, oxo, hydroxycarbonyl,alkoxycarbonyl, acylamino, carbamoyl, alkylcarbamoyl,dihydroxyphosphoryloxy and dialkoxyphosphoryloxy groups; or c) a groupof formula—(CH₂)_(n)—R⁶ n is an integer from 0 to 4 and R⁶ represents a 3- to7-membered aromatic or non-aromatic cyclic group containing from 0 to 4heteroatoms chosen from N, O and S, wherein said 3- to 7-memberedaromatic or non-aromatic cyclic group is optionally bridged and/or fusedto another 3- to 7-membered aromatic or non-aromatic cyclic groupcontaining from 0 to 4 heteroatoms chosen from N, O and S; and whereineach of the cyclic groups in the moiety R⁶ is independently optionallysubstituted by one or more R⁷ substituents; R⁷ represents a group chosenfrom halogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, hydroxy, alkylenedioxy,alkoxy, alkylthio, amino, monoalkylamino, dialkylamino, nitro, cyano,oxo, hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl,alkylcarbamoyl, dihydroxyphosphoryloxy and dialkoxyphosphoryloxy groups;wherein each of the hydrocarbon chains and each of the cyclic moietiesin R⁷ is independently optionally substituted by one or more further R⁸substituents; R⁸ represents a group chosen from halogen, hydroxy, oxo,cyano, alkyl, difluoromethyl, trifluoromethyl, alkoxy, alkylenedioxy,alkylthio, acylamino, carbamoyl, alkylcarbamoyl, dihydroxyphosphoryloxy,dialkoxyphosphoryloxy, hydroxyalkoxy, phenyl, alkoxycarbonyl, amino,monoalkylamino, dialkylamino, and hydroxycarbonyl groups; R³ representsa hydrogen or halogen atom, or a nitro, alkoxycarbonyl or alkyl group;wherein the alkyl group is optionally substituted by one or moresubstituents chosen from hydroxy, alkoxy, alkylthio, amino,monoalkylamino, dialkylamino, hydroxycarbonyl, alkoxycarbonyl,acylamino, carbamoyl and alkylcarbamoyl groups; R⁴ represents: a)hydrogen; b) a group of formula —(CH₂)_(n)—R⁶ wherein n is 0, 1 or 2 andR⁶ is a 5- to 6-membered heteroaryl or heterocyclyl group containing upto 2 heteroatoms chosen from N, O and S, wherein R⁶ is optionallysubstituted by a R⁷ substituent chosen from alkyl, alkoxy, arylalkyl orheteroarylalkyl groups, wherein each of the aryl and heteroaryl moietiesof these arylalkyl and heteroarylalkyl R⁷ substituents is independentlyoptionally substituted by 1 or 2 further R⁸ substituents chosen fromhalogen, cyano, alkyl, trifluoromethyl, alkoxy and alkylenedioxy; or c)an alkyl group, which is optionally substituted by 1 or 2 substituentschosen from amino, monoalkylamino, dialkylamino, —OR⁶ and —SR⁶substituents, wherein R⁶ is a 5- or 6-membered heteroaryl groupcontaining 1 or 2 heteroatoms, and is optionally substituted by one ormore R⁷ substituents chosen from hydroxy, halogen, amino,monoalkylamino, dialkylamino, cyano, hydroxycarbonyl, alkoxycarbonyl,alkoxy, alkylenedioxy and alkylthio; and wherein the alkyl chains ofeach of the said monoalkylamino and dialkylamino substituents areindependently optionally substituted by 1 or 2 further substituentschosen from a hydroxy group and a group of formula —(CH₂)_(n)—R⁶,wherein n is an integer from 0 to 4 and R⁶ is an aryl group; R⁵ ishydrogen, a group of formula —(CH₂)_(n)R⁶ or a hydrocarbon chain chosenfrom alkyl, alkenyl and alkynyl, wherein said hydrocarbon chain isoptionally substituted by one or more groups chosen from —(CH₂)_(n)—R⁶and —O—(CH₂)_(n)—R⁶; wherein each R⁶ is independently a phenyl or apyridyl group, and wherein each R⁶ is independently optionallysubstituted by one or more substituents chosen from halogen, hydroxy,alkyl, alkoxy and alkylthio groups; or an N-oxide or a pharmaceuticallyacceptable salt thereof.
 8. A compound according to claim 1, wherein R⁴and R⁵ form, together with the nitrogen atom to which they are attached,an optionally bridged 5- to 7-membered aromatic or non-aromatic cyclicgroup, which contains up to two nitrogen atoms, and which is optionallysubstituted by a group of formula —(CH₂)_(n)—R⁶ or by a R⁷ substituentchosen from alkyl, alkenyl and alkynyl chains; wherein each of saidalkyl, alkenyl and alkynyl chains is independently optionallysubstituted by one or more groups of formula —(CH₂)_(n)—R⁶ or R⁸substituents chosen from hydroxy, halogen, alkoxy, alkylthio, amino,monoalkylamino, and dialkylamino groups; wherein each of the alkylchains in these R⁸ substituents is independently optionally substitutedby one or more further substituents chosen from a group of formula—(CH₂)_(n)—R⁶, and hydroxy, halogen, alkoxy, alkylthio, amino,monoalkylamino and dialkylamino groups; wherein each of the R⁶ groups isindependently chosen from each other.
 9. A compound according to claim1, wherein R⁴ and R⁵ form, together with the N atom to which they areattached, a 5-, 6- or 7-membered saturated heterocyclic group, whichcontains 1 or 2 nitrogen atoms and which optionally carries a bridgingalkylene group, wherein said saturated heterocyclic cyclic group isoptionally substituted by a group of formula —(CH₂)_(n)—R⁶ wherein n is0, 1 or 2 and R⁶ is a 5- or 6-membered aromatic or non-aromatic ringcontaining 0, 1 or 2 heteroatoms chosen from N, O and S, or by a R⁷substituent chosen from alkyl and alkenyl groups, wherein the group R⁶is optionally substituted by 1, 2 or 3 further substituents chosen fromhaloalkyl, alkyl, alkoxy, alkylenedioxy, cyano and halogen groups, andthe said R⁷ substituent optionally substituted by 1 or 2 phenylsubstituents.
 10. A compound according to claim 1 chosen from:4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]benzenesulfonamide;4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(6methoxypyridin-2-yloxy)ethyl]benzenesulfonamide;6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;6-{4-[4-(4-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;6-{4-[4-(3-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;1-Methyl-3-propyl-6-[4-(4-pyridin-2-ylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione,4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide;4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide;4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylbenzenesulphonamide;4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-yl)benzenesulphonamide;6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;N-(1-Benzylpiperidin-4-yl)-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide;4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(4-fluorobenzyl)piperidin-4-yl]benzenesulphonamide;or a pharmaceutically acceptable salt or an N-oxide thereof.
 11. Aprocess for producing a compound of formula I as claimed in claim 1,comprising reacting a sulphonyl chloride of formula II

with the corresponding amine III

and optionally converting the product of the reaction into thecorresponding N-oxide or pharmaceutically acceptable salt thereof.
 12. Aprocess according to claim 11, wherein the sulphonyl chloride of formulaII is obtained from the corresponding compound of formula IV:

by reaction with an excess of chlorosulphonic acid.
 13. A compound offormula II

wherein R¹ and R² each independently represents: a) a hydrogen atom; b)a hydrocarbon chain chosen from an alkyl, alkenyl and alkynyl group,wherein said hydrocarbon chain is optionally substituted by one or moresubstituents chosen from halogen, hydroxy, alkoxy, alkylthio, amino,monoalkylamino, dialkylamino, cyano, oxo, hydroxycarbonyl,alkoxycarbonyl, acylamino, carbamoyl, alkylcarbamoyl,dihydroxyphosphoryloxy and dialkoxyphosphoryloxy groups; or c) a groupof formula—(CH₂)_(n)—R⁶ n is an integer from 0 to 4 and R⁶ represents a 3- to7-membered aromatic or non-aromatic cyclic group containing from 0 to 4heteroatoms chosen from N, O and S, wherein said 3- to 7-memberedaromatic or non-aromatic cyclic group is optionally bridged and/or fusedto another 3- to 7-membered aromatic or non-aromatic cyclic groupcontaining from 0 to 4 heteroatoms chosen from N, O and S; wherein eachof the cyclic groups in the moiety R⁶ is independently optionallysubstituted by one or more R⁷ substituents; R⁷ represents a group chosenfrom halogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, hydroxy, alkylenedioxy,alkoxy, alkylthio, amino, monoalkylamino, dialkylamino, nitro, cyano,oxo, hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl,alkylcarbamoyl, dihydroxyphosphoryloxy and dialkoxyphosphoryloxy groups;wherein each of the hydrocarbon chains and each of the cyclic moietiesin R⁷ is independently optionally substituted by one or more further R⁸substituents; R⁸ represents a group chosen from halogen, hydroxy, oxo,cyano, alkyl, difluoromethyl, trifluoromethyl, alkoxy, alkylenedioxy,alkylthio, acylamino, carbamoyl, alkylcarbamoyl, dihydroxyphosphoryloxy,dialkoxyphosphoryloxy, hydroxyalkoxy, phenyl, alkoxycarbonyl, amino,monoalkylamino, dialkylamino and hydroxycarbonyl groups; R³ represents ahydrogen or halogen atom, or a nitro, alkoxycarbonyl or alkyl group;wherein the alkyl group is optionally substituted by one or moresubstituents chosen from hydroxy, alkoxy, alkylthio, amino,monoalkylamino, dialkylamino, hydroxycarbonyl, alkoxycarbonyl,acylamino, carbamoyl and alkylcarbamoyl groups; or an N-oxide or apharmaceutically acceptable salt thereof.
 14. A pharmaceuticalcomposition comprising a compound as claimed in claim 1 and apharmaceutically acceptable diluent or carrier.